Pulmonary fibrotic response to aspiration of multi-walled carbon nanotubes

Abstract

BackgroundMulti-walled carbon nanotubes (MWCNTs) are new manufactured nanomaterials with a wide spectrum of commercial applications. To address the hypothesis that MWCNTs cause persistent pulmonary pathology, C57BL/6J mice were exposed by pharyngeal aspiration to 10, 20, 40 or 80 μg of MWCNTs (mean dimensions of 3.9 μm × 49 nm) or vehicle. Lungs were preserved at 1, 7, 28 and 56 days post- exposure to determine the potential regions and target cells for impact by MWCNT lung burden. Morphometric measurement of Sirius Red staining was used to assess the connective tissue response.ResultsAt 56 days post-exposure, 68.7 ± 3.9, 7.5 ± 1.9 and 22.0 ± 5.1 percent (mean ± SE, N = 8) of the MWCNT lung burden were in alveolar macrophages, alveolar tissue and granulomatous lesions, respectively. The subpleural tissues contained 1.6% of the MWCNT lung burden. No MWCNTs were found in the airways at 7, 28 or 56 days after aspiration The connective tissue in the alveolar interstitium demonstrated a progressive increase in thickness over time in the 80 μg exposure group (0.12 ± 0.01, 0.12 ± 0.01, 0.16 ± 0.01 and 0.19 ± 0.01 μm for 1, 7, 28 and 56 days post-exposure (mean ± SE, N = 8)). Dose-response determined at 56 days post-exposure for the average thickness of connective tissue in alveolar septa was 0.11 ± 0.01, 0.14 ± .02, 0.14 ± 0.01, 0.16 ± 0.01 and 0.19 ± 0.01 μm (mean ± SE, N = 8) for vehicle, 10, 20, 40 and 80 μg dose groups, respectively.ConclusionsThe distribution of lung burden was predominately within alveolar macrophages with approximately 8% delivery to the alveolar septa, and a smaller but potentially significant burden to the subpleural tissues. Despite the relatively low fraction of the lung burden being delivered to the alveolar tissue, the average thickness of connective tissue in the alveolar septa was increased over vehicle control by 45% in the 40 μg and 73% in the 80 μg exposure groups. The results demonstrate that MWCNTs have the potential to produce a progressive, fibrotic response in the alveolar tissues of the lungs. However, the increases in connective tissue per μg dose of MWCNTs to the interstitium are significantly less than those previously found for single-walled carbon nanotubes (SWCNTs).

Identification of Metal Oxide Nanoparticles in Histological Samples by Enhanced Darkfield Microscopy and Hyperspectral Mapping

“…For example, individual nanotubes can be observed in lungs during inhalation of doses as low as 40 µg in a 20-30 g rat 25 . Figure 3 demonstrates this in histological skin samples: while some particles are readily obvious in the darkfield optical image (column 2), others are detected using hyperspectral imaging (column 3) that might have been missed using brightfield microscopy (column 1) or other methods.…”

Occupational Nanosafety Considerations for Carbon Nanotubes and Carbon Nanofibers

“…17 Morphometric analysis indicates that a greater fraction of alveolar MWCNTs are phagocytized than SWCNTs, while a greater fraction of SWCNTs enter the alveolar interstitium. 18 This results in a greater fibrotic reaction to an equal lung burden of SWCNTs compared with MWCNTs. 18 Recently, Murray et al 19 reported that aspiration of CNFs in a mouse model also resulted in transient inflammation and damage and persistent fibrosis.…”

“…18 This results in a greater fibrotic reaction to an equal lung burden of SWCNTs compared with MWCNTs. 18 Recently, Murray et al 19 reported that aspiration of CNFs in a mouse model also resulted in transient inflammation and damage and persistent fibrosis. The fibrotic potency (on a mass lung burden basis) was SWCNTs > CNFs = asbestos.…”

Assessing the impact of the physical properties of industrially produced carbon nanotubes on their interaction with human primary macrophages in vitro

“…In addition to the landmark study by Maynard and colleagues in 2004 which estimated workers within a CNT manufacturing plant to be exposed to 53 µg/m 3 of aerosolized CNTs [5], only a recent NIOSH report has managed to suggest a human CNT exposure limit of 1 µg/m 3 (previously considered as 7 µg/m 3 [14]). These limits however, were founded upon on a number of high-profile studies using, debatably, overload doses in vivo [15][16][17][18][19][20][21][22]. It is imperative therefore that these findings are confirmed within a realistic occupational setting (i.e., CNT manufacturing plant).…”